Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT

Abstract

Background To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex. Methods The phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex. Results Efficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P < 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27− subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively. Conclusions Secukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (−) subgroups. Male patients had higher relative responses than female patients. Trial registration ClinicalTrials.gov, NCT02696031. Registered on 02 March 2016

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study

“… 46 Similarly, the PREVENT study performed a subgroup analysis, which revealed that male axSpA patients treated with SEC had higher relative responses than female patients with ASAS40 response rates of 51.2% and 31.7%, respectively. 47 As far as time-to-SEC discontinuation is concerned, male sex appeared to be protective against drug discontinuation. This finding is in accordance with other reports concerning a higher discontinuation rate of first- and second-line biologics among female axSpA.…”

Sex-associated and gender-associated differences in the diagnosis and management of axial spondyloarthritis: addressing the unmet needs of female patients

“…Newly published subanalyses for secukinumab in nr-axSpA show that, while clinically meaningful efficacy was seen in both male and female patients, higher responses were consistently observed in men across all outcome measures. 29 Sufficiently powered studies are needed to further investigate these findings. Comorbidities may have an impact on disease activity, disease assessment and treatment response.…”

Current differentiation between radiographic and non-radiographic axial spondyloarthritis is of limited benefit for prediction of important clinical outcomes: data from a large, prospective, observational cohort

“…Indeed, posthoc subgroup analyses in nr-axSpA patients treated with secukinumab have demonstrated that patients with Spondyloarthritis Spondyloarthritis Spondyloarthritis higher level of SIJ inflammation on baseline MRI expebetter efficacy in comparison to those with more limited SIJ inflammatory lesions. 47 The opportunity to accurately detect patients with axSpA with short disease duration and marginal functional impairment bears the potential to select patients with nr-axSpA with early disease that hopefully will demonstrate better treatment responses than those with r-axSpA. 48 Mechanical SIJ strain induced during recreational and athletic activities or during pregnancy may mimic inflammation, 26 27 thus challenging the diagnosis and classification of axSpA in an unknown proportion of patients, potentially contributing to the lower treatment responses in nr-axSpA.…”

“…It can reasonably be hypothesised that a more detailed SIJ MRI evaluation with regard to the amount and intensity of inflammation as well as to the presence of different structural lesions would increase its diagnostic capacity and allow a more accurate detection of patients with early axSpA. Indeed, posthoc subgroup analyses in nr-axSpA patients treated with secukinumab have demonstrated that patients with a higher level of SIJ inflammation on baseline MRI experienced better efficacy in comparison to those with more limited SIJ inflammatory lesions 47. The opportunity to accurately detect patients with axSpA with short disease duration and marginal functional impairment bears the potential to select patients with nr-axSpA with early disease that hopefully will demonstrate better treatment responses than those with r-axSpA 48…”